Long non-coding RNAs are defined as transcripts larger than 200nucleotides but without protein-coding potential. There is growingevidence of the important role of long non-coding RNAs in cancerinitiation, development and progression. In this study, we sought to eval-uate the long non-coding RNA expression profile of patients with cyto-genetically normal acute myeloid leukemia (AML). RNA-sequencing of40 cytogenetically normal AML patients allowed us to quantify 11,036long non-coding RNAs. Among these, more than 8000 were previouslyundescribed long non-coding RNAs. Using unsupervised analysis, weobserved a specific long non-coding RNA expression profile dependenton the mutational status of the NPM1gene. Statistical analysis allowedus to identify a minimal set of 12 long non-coding RNAs capable of dis-criminating NPM1-mutated from NPM1-wild-type patients. Theseresults were validated by qRT-PCR on an independent cohort composedof 134 cytogenetically normal AML patients. Furthermore, we have iden-tified one putative biomarker, the long non-coding RNA XLOC_109948whose expression pattern predicts clinical outcome. Interestingly, lowXLOC_109948 expression indicates a good prognosis especially forNPM1-mutated patients. Transient transfection of GapmeR againstXLOC_109948 in NPM1-mutated OCI-AML3 cell line treated with Ara-C or ATRA enhances apoptosis suggesting XLOC_109948 plays a role indrug sensitivity. This study improves our knowledge of the long non-coding RNA transcriptome in cytogenetically normal AML patients. Weobserved a distinct long non-coding RNA expression profile in patientswith the NPM1mutation. The newly identified XLOC_109948 longnon-coding RNA emerged as a strong prognostic factor able to betterstratify NPM1-mutated patients.

Long non-coding RNA expression profile in cytogenetically normal acute myeloid leukemia identifies a distinct signature and a new biomarker in NPM1-mutated patients

Martelli, Maria Paola;Falini, Brunangelo;
2017

Abstract

Long non-coding RNAs are defined as transcripts larger than 200nucleotides but without protein-coding potential. There is growingevidence of the important role of long non-coding RNAs in cancerinitiation, development and progression. In this study, we sought to eval-uate the long non-coding RNA expression profile of patients with cyto-genetically normal acute myeloid leukemia (AML). RNA-sequencing of40 cytogenetically normal AML patients allowed us to quantify 11,036long non-coding RNAs. Among these, more than 8000 were previouslyundescribed long non-coding RNAs. Using unsupervised analysis, weobserved a specific long non-coding RNA expression profile dependenton the mutational status of the NPM1gene. Statistical analysis allowedus to identify a minimal set of 12 long non-coding RNAs capable of dis-criminating NPM1-mutated from NPM1-wild-type patients. Theseresults were validated by qRT-PCR on an independent cohort composedof 134 cytogenetically normal AML patients. Furthermore, we have iden-tified one putative biomarker, the long non-coding RNA XLOC_109948whose expression pattern predicts clinical outcome. Interestingly, lowXLOC_109948 expression indicates a good prognosis especially forNPM1-mutated patients. Transient transfection of GapmeR againstXLOC_109948 in NPM1-mutated OCI-AML3 cell line treated with Ara-C or ATRA enhances apoptosis suggesting XLOC_109948 plays a role indrug sensitivity. This study improves our knowledge of the long non-coding RNA transcriptome in cytogenetically normal AML patients. Weobserved a distinct long non-coding RNA expression profile in patientswith the NPM1mutation. The newly identified XLOC_109948 longnon-coding RNA emerged as a strong prognostic factor able to betterstratify NPM1-mutated patients.
2017
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/1436795
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